Replacement heart valve

ABSTRACT

A prosthetic heart valve has leaflets made of a thin and flexible material. The side edges of adjacent leaflets are sewn together so as to form a substantially tubular valve structure having an in-flow end and an out-flow end. Each of the leaflets is adapted to flex inwardly into and out of engagement with another leaflet so as to close and open the valve in response to force by blood pressure. The leaflets are configured so that a portion of the inner face of each leaflet is in a facing relationship with a portion of the inner face of an adjacent leaflet.

RELATED APPLICATIONS

[0001] This is a divisional application, based on prior U.S. applicationSer. No. 10/153,286, filed May 21, 2002, which is a continuation of U.S.Ser. No. 09/924,970, filed Aug. 7, 2001, which is a continuation of U.S.Ser. No. 09/536,229, filed on Mar. 27, 2000, now U.S. Pat. No.6,270,526, which is a division of U.S. Ser. No. 09/288,998, filed onFeb. 3, 1999, now U.S. Pat. No. 6,092,529, which is a continuation ofU.S. Ser. No. 08/748,055, filed on Nov. 13, 1996, which is a division ofU.S. Ser. No. 08/459,979, filed on Jun. 2, 1995, now U.S. Pat. No.5,713,950, which is a division of U.S. Ser. No. 08/146,938, filed Nov.1, 1993, now U.S. Pat. No. 5,480,424. The entire disclosure of each ofthe aforementioned patents and applications are hereby incorporated byreference in its entirety as if set forth fully herein.

BACKGROUND OF THE INVENTION

[0002] 1. Field of the Invention

[0003] This invention is in the field of replacement heart valves.

Anatomy of Normal Heart Valves

[0004] There are four valves in the heart that serve to direct the flowof blood through the two sides of the heart in a forward direction. Onthe left (systemic) side of the heart are: 1) the mitral valve, locatedbetween the left atrium and the left ventricle, and 2) the aortic valve,located between the left ventricle and the aorta. These two valvesdirect oxygenated blood coming from the lungs, through the left side ofthe heart, into the aorta for distribution to the body. On the right(pulmonary) side of the heart are: 1) the tricuspid valve, locatedbetween the right atrium and the right ventricle, and 2) the pulmonaryvalve, located between the right ventricle and the pulmonary artery.These two valves direct de-oxygenated blood coming from the body,through the right side of the heart, into the pulmonary artery fordistribution to the lungs, where it again becomes re-oxygenated to beginthe circuit anew.

[0005] All four of these heart valves are passive structures that theydo not themselves expend any energy and do not perform any activecontractile function. They consist of moveable “leaflets” that aredesigned simply to open and close in response to differential pressureson either side of the valve. The mitral and tricuspid valves arereferred to as “atrioventricular valves” because of their being situatedbetween an atrium and ventricle on each side of the heart. The mitralvalve has two leaflets and the tricuspid valve has three. The aortic andpulmonary valves are referred to as “semilunar valves” because of theunique appearance of their leaflets, which are more aptly termed “cusps”and are shaped somewhat like a half-moon. The aortic and pulmonaryvalves each have three cusps.

[0006] Since the physiological structures of native mitral and tricuspidvalves and native aortic and pulmonary valves are important to thisinvention, they are depicted in FIG. 1, which contains a cross-sectionalcutaway depiction of a normal human heart 100 (shown next to heart 100is a segment of tubular tissue 200 which will be used to replace themitral valve, as described below). The left side of heart 100 containsleft atrium 110, left ventricular chamber 112 positioned between leftventricular wall 114 and septum 116, aortic valve 118, and mitral valveassembly 120. The components of the mitral valve assembly 120 includethe mitral valve annulus 121, which will remain as a roughly circularopen ring after the leaflets of a diseased or damaged valve have beenremoved; anterior leaflet 122 (sometimes called the aortic leaflet,since it is adjacent to the aortic region); posterior leaflet 124; twopapillary muscles 126 and 128 which are attached at their bases to theinterior surface of the left ventricular wall 114; and multiple chordaetendineae 13 which couple the mitral valve leaflets 122 and 124 to thepapillary muscles 126 and 128. There is no one-to-one chordal connectionbetween the leaflets and the papillary muscles; instead, numerouschordae are present, and chordae from each papillary muscle 126 and 128attach to both of the valve leaflets 122 and 124.

[0007] The other side of the heart contains the right atrium 150, aright ventricular chamber 152 bounded by right ventricular wall 154 andseptum 116, and a tricuspid valve assembly 160. The tricuspid valveassembly 160 comprises a valve annulus 162, three leaflets 164,papillary muscles 170 attached to the interior surface of the rightventricular wall 154, and multiple chordae tendineae 180 which couplethe tricuspid valve leaflets 164 to the papillary muscles 170-174.

[0008] As mentioned above, the mitral valve leaflets 122 and 124, andtricuspid valve leaflets 164 are all passive structures; they do notthemselves expend any energy and do not perform any active contractilefunction. They are designed to simply open and close in response todifferential pressures on either side of the leaflet tissue. When theleft ventricular wall 114 relaxes so that the ventricular chamber 112enlarges and draws in blood, the mitral valve 120 opens (i.e., theleaflets 122 and 124 separate). Oxygenated blood flows in a downwarddirection through the valve 120, to fill the expanding ventricularcavity. Once the left ventricular cavity has filled, the left ventriclecontracts, causing a rapid rise in the left ventricular cavitarypressure. This causes the mitral valve 120 to close (i.e., the leaflets122 and 124 re-approximate) while the aortic valve 118 opens, allowingthe oxygenated blood to be ejected from the left ventricle into theaorta. The chordae tendineae 132 of the mitral valve prevent the mitralleaflets 122 and 124 from prolapsing back into the left atrium 110 whenthe left ventricular chamber 114 contracts.

[0009] The three leaflets, chordae tendineae, and papillary muscles ofthe tricuspid valve function in a similar manner, in response to thefilling of the right ventricle and its subsequent contraction.

[0010] The cusps of the aortic valve also respond passively to pressuredifferentials between the left ventricle and the aorta. When the leftventricle contracts, the aortic valve cusps open to allow the flow ofoxygenated blood from the left ventricle into the aorta. When the leftventricle relaxes, the aortic valve cusps reapproximate to prevent theblood which has entered the aorta from leaking (regurgitating) back intothe left ventricle. The pulmonary valve cusps respond passively in thesame manner in response to relaxation and contraction of the rightventricle in moving de-oxygenated blood into the pulmonary artery andthence to the lungs for re-oxygenation. Neither of these semilunarvalves has associated chordae tendineae or papillary muscles.

[0011] In summary, with relaxation and expansion of the ventricles(diastole), the mitral and tricuspid valves open, while the aortic andpulmonary valves close. When the ventricles contract (systole), themitral and tricuspid valve close and the aortic and pulmonary valvesopen. In this manner, blood is propelled through both sides of theheart.

[0012] The anatomy of the heart and the structure and terminology ofheart valves are described and illustrated in detail in numerousreference works on anatomy and cardiac surgery, including standard textssuch as Surgery of the Chest (Sabiston and Spencer, eds., SaundersPubl., Philadelphia) and Cardiac Surgery by Kirklin and Barrett-Boyes.

Pathology and Abnormalities of Heart Valves

[0013] Heart valves may exhibit abnormal anatomy and function as aresult of congenital or acquired valve disease. Congenital valveabnormalities may be so severe that emergency surgery is required withinthe first few hours of life, or they may be well-tolerated for manyyears only to develop a life-threatening problem in an elderly patient.Acquired valve disease may result from causes such as rheumatic fever,degenerative disorders of the valve tissue, bacterial or fungalinfections, and trauma.

[0014] Since heart valves are passive structures that simply open andclose in response to differential pressures on either side of theparticular valve, the problems that can develop with valves can beclassified into two categories: 1) stenosis, in which a valve does notopen properly, or 2) insufficiency (also called regurgitation), in whicha valve does not close properly. Stenosis and insufficiency may occurconcomitantly in the same valve or in different valves. Both of theseabnormalities increase the workload placed on the heart, and theseverity of this increased stress on the heart and the patient, and theheart's ability to adapt to it, determine whether the abnormal valvewill have to be surgically replaced (or, in some cases, repaired) ornot.

[0015] In addition to stenosis and insufficiency of heart valves,surgery may also be required for certain types of bacterial or fungalinfections in which the valve may continue to function normally, butnevertheless harbors an overgrowth of bacteria (a so-called“vegetation”) on the leaflets of the valve that may flake off(“embolize”) and lodge downstream in a vital artery. If such vegetationsare on the valves of the left side (i.e., the systemic circulation side)of the heart, embolization results in sudden loss of the blood supply tothe affected body organ and immediate malfunction of that organ. Theorgan most commonly affected by such embolization is the brain, in whichcase the patient suffers a stroke. Thus, surgical replacement of eitherthe mitral or aortic valve (left-sided heart valves) may be necessaryfor this problem even though neither stenosis nor insufficiency ofeither valve is present. Likewise, bacterial or fungal vegetations onthe tricuspid valve may embolize to the lungs (resulting in a lungabscess) and therefore, may require replacement of the tricuspid valveeven though no tricuspid valve stenosis or insufficiency is present.With the exception of congenital pulmonary valve stenosis orinsufficiency, it is unusual for a patient to develop an abnormality ofthe pulmonary valve that is significant enough to require surgicalrepair or replacement.

[0016] Currently, surgical repair of mitral and tricuspid valves ispreferred over total valve replacement when possible, although often thevalves are too diseased to repair and must be replaced. Mostabnormalities of the aortic valve require replacement, although someefforts are now being made to repair insufficient aortic valves inselected patients. Valve repair and valve replacement surgery isdescribed and illustrated in numerous books and articles, including thetexts cited herein.

Current Options for Heart Valve Replacement

[0017] If a heart valve must be replaced, there are currently severaloptions available, and the choice of a particular type of prosthesis(i.e., artificial valve) depends on factors such as the location of thevalve, the age and other specifics of the patient, and the surgeon'sexperiences and preferences. Available prostheses include threecategories of valves or materials: mechanical valves, tissue valves, andaortic homograft valves. These are briefly discussed below; they areillustrated and described in detail in texts such as Replacement CardiacValves, edited by E. Bodnar and R. Frater (Pergamon Press, New York,1991).

Artificial Mechanical Valves

[0018] Mechanical valves include caged-ball valves (such asStarr-Edwards valves), bi-leaflet valves (such as St. Jude valves), andtilting disk valves (such as Medtronic-Hall or omniscience valves).Caged ball valves usually are made with a ball made of a silicone rubber(Silastic™) inside a titanium cage, while bi-leaflet and tilting diskvalves are made of various combinations of pyrolytic carbon andtitanium. All of these valves are attached to a cloth (usually Dacron™)sewing ring so that the valve prosthesis can be sutured to the patient'snative tissue to hold the artificial valve in place postoperatively. Allof these mechanical valves can be used to replace any of the heart'sfour valves. No other mechanical valves are currently approved for useby the FDA in the U.S.A.

[0019] The main advantage of mechanical valves is their long-termdurability. Their main disadvantage is that they require the patient totake systemic anticoagulation drugs for the rest of his or her life,because of the propensity of mechanical valves to cause blood clots toform on them. If such blood clots form on the valve, they may precludethe valve from opening or closing correctly or, more importantly, theblood clots may disengage from the valve and embolize to the brain,causing a stroke. The anticoagulant drugs that are necessary to preventthis are expensive and potentially dangerous in that they may causeabnormal bleeding which, in itself, can cause a stroke if the bleedingoccurs within the brain.

[0020] In addition to the mechanical valves available for implantationtoday, a number of other valve designs are described and illustrated ina chapter called “Extinct Cardiac Valve Prostheses,” at pages 307-332 ofReplacement Cardiac Valves (Bodnar and Frater, cited above). Two of the“extinct” valves which deserve attention as prior art in the subjectinvention are the McGoon valve (pp. 319-320) and the Roe-Moore valve(pp. 320-321). Both of these involve flexible leaflets made of anelastomer or cloth coated with polytetrafluoroethylene (PTFE, widelysold under the trademark TEFLON), mounted inside a cylindrical stent.Although both were tested in humans, they were never commercialized andapparently are not being actively studied or developed today.

Artificial Tissue Valves

[0021] Most tissue valves are constructed by sewing the leaflets of pigaortic valves to a stent (to hold the leaflets in proper position), orby constructing valve leaflets from the pericardial sac (which surroundsthe heart) of cows or pigs and sewing them to a stent. The stents may berigid or slightly flexible and are covered with cloth (usually asynthetic material sold under the trademark Dacron™) and attached to asewing ring for fixation to the patient's native tissue. The porcine orbovine tissue is chemically treated to alleviate any antigenicity (i.e.,to reduce the risk that the patient's body will reject the foreigntissue). These tri-leaflet valves may be used to replace any of theheart's four valves. The only tissue valves currently approved by theFDA for implantation in the U.S.A. are the Carpentier-Edwards PorcineValve, the Hancock Portcine Valve, and the Carpentier-EdwardsPericardial Valve.

[0022] The main advantage of tissue valves is that they do not causeblood clots to form as readily as do the mechanical valves, andtherefore, they do not absolutely require systemic anticoagulation.Nevertheless, many surgeons do anticoagulate patients who have any typeof artificial mitral valve, including tissue valves. The majordisadvantage of tissue valves is that they lack the long-term durabilityof mechanical valves. Tissue valves have a significant failure rate,usually appearing at approximately 8 years following implantation,although preliminary results with the new commercial pericardial valvessuggest that they may last longer. One cause of these failures isbelieved to be the chemical treatment of the animal tissue that preventsit from being antigenic to the patient. In addition, the presence of thestent and sewing ring prevents the artificial tissue valve from beinganatomically accurate in comparison to a normal heart valve, even in theaortic valve position.

Homograft Valves

[0023] Homograft valves are harvested from human cadavers. They are mostcommonly aortic valves but also occasionally include pulmonic valves.These valves are specially prepared and frozen in liquid nitrogen, wherethey are stored for later use in adults for aortic valve replacement, orin children for pulmonary valve replacement. A variant occasionallyemployed for aortic valve replacement is to use the patient's ownpulmonary valve (an autograft) to replace a diseased aortic valve,combined with insertion of an aortic (or pulmonary) homograft from acadaver to replace the excised pulmonary valve (this is commonly calleda “Ross procedure”).

[0024] The advantage of aortic homograft valves is that they, appear tobe as durable as mechanical valves and yet they do not promote bloodclot formation and therefore, do not require anticoagulation. The maindisadvantage of these valves is that they are not available insufficient numbers to satisfy the needs of patients who need new aorticor pulmonary valves. They also cannot be used to replace either themitral valve or tricuspid valve. In addition, they are extremelyexpensive and much more difficult to implant than either mechanical ortissue valves. The difficulty in implantation means that the operativerisk with a homograft valve is greater in a given patient than it iswith either a mechanical or tissue valve. An additional problem is thatin June 1992, the FDA reclassified homograft valves as an experimentaldevice, so they are no longer available on a routine basis.

Principles of Artificial Heart Valve Construction

[0025] All artificial heart valves are designed to optimize three majorphysiologic characteristics and one practical consideration. The threemajor physiologic characteristics are (1) hemodynamic performance, (2)thrombogenicity, and (3) durability. The practical considerationinvolves ease of surgical implantation.

[0026] Multiple factors impact on each of these potential problems inthe development of artificial valves. As a result, the advantage ofartificial valve A over artificial valve B in one area is typicallycounterbalanced by valve B's advantage in another area. If oneartificial heart valve were clearly superior in all aspects to all otherartificial valves in all four of these areas, it would be the onlyartificial valve used.

Artificial Mechanical Valves

[0027] The hemodynamic performance of mechanical heart valves has beensatisfactory but not optimal, especially in the smaller sizes. Allpreviously constructed mechanical heart valves have had some type ofobstructing structure within the flow orifice of the valve when thevalve is in the open position. For example, bi-leaflet valves, such asthe St. Jude valve, have two bars across the orifice and in addition,the leaflets themselves are within the orifice when the valve is in theopen position. Single-leaflet disc valves, such as the Medtronic-Hallvalve, have a central bar and strut mechanism that keep the leaflet inplace. The Bjork-Shiley valves have either one or two struts that spanthe valve orifice in addition to the partially-opened disc itself. Theomniscience valve has the partially opened disk itself in the valveorifice when open, and the Starr-Edwards caged-ball valve has both theball and the cage within the flow orifice of the valve in the openposition. All of these structures decrease the hemodynamic performanceof the mechanical valves.

[0028] Such obstructions also interfere with the normal flow patternswithin and around the mechanical valve and therefore, promotethrombosis. More importantly, all artificial surfaces are thrombogenic(clot-promoting) to a greater or lesser degree. The only completelynon-thrombogenic (non-clot-promoting) surface that exists is the layerof viable endothelial cells that line the interior of all the body'svascular surfaces, including the inside of the heart chambers and thenative valve leaflets. Therefore, any metal or plastic material, nomatter how highly polished, will have some level of thrombogenicityunless the surface of the artificial material can be covered withendothelial cells. It is for this reason that all patients withartificial mechanical heart valves must be permanently anticoagulated.

[0029] The major advantage of mechanical valves over tissue valves islong-term durability. Mechanical valve construction has been based onsophisticated engineering principles that have proven to be sound interms of providing devices that are extremely resistant to wear andstructural failure. Nevertheless, structural failure of mechanicalvalves does occur and it is the major reason for the recent withdrawalfrom the market of two commercially available mechanical valves (theBjork-Shiley Concavo-Convex™ single disc valve and the Duramedics™bi-leaflet valve).

Artificial Tissue Valves

[0030] Under the best of circumstances (i.e., replacement of the aorticvalve), the construction of artificial tissue valves has been based onthe concept that if the artificial valve can be made to approximate theanatomy (form) of the native valve, then the physiology (function) ofthe artificial valve will also approximate that of the native valve.This is the concept that “Function Follows Form.” For example, themanufacturers of all artificial porcine valves first re-create the formof a native human aortic valve by: 1) harvesting a porcine aortic valve,2) fixing it in glutaraldehyde to eliminate antigenicity, and 3)suturing the porcine valve to a stent to hold the three leaflets inplace. In other words, the primary goal in the construction of theseartificial valves is to reproduce the form of the human aortic valve asclosely as possible. The assumption is made that if the artificial valvecan be made to look like the human aortic valve, it will function likethe human aortic valve (i.e., proper function will follow proper form).The same assumption is also followed for commercially availablepericardial valves.

[0031] In the case of mitral or tricuspid valve replacement, even thedubious concept of “function follows form” has been discarded since thesame artificial valves that are designed to look like the aortic valveare used to replace the mitral and tricuspid-valves. In other words, noattempt at all is made to reproduce even the form of these nativevalves, much less so their function.

[0032] Thus, in the case of artificial valves to be used for aorticvalve replacement, the dubious concept of “function follows form” hasdictated the construction of all artificial tissue valves during the 30years of their development and use. Even worse, no discernableunderlying concept at all has been used in terms of the artificialvalves used to replace the mitral and tricuspid valves.

[0033] The “Function Follows Form” concept has several limitations andappears to be a fundamental shortcoming which underlies the presentconstruction of all artificial tissue valves. In the first place, itsimply is not possible to recreate the exact anatomy (form) of a nativeheart valve utilizing present techniques. Although homograft (humancadaver) and porcine aortic valves have the gross appearance of nativeaortic valves, the fixation process (freezing with liquid nitrogen, andchemical treatment, respectively) alters the histologic (microscopic)characteristics of the valve tissue. Porcine and bovine pericardialvalves not only require chemical preparation (usually involving fixationwith glutaraldehyde), but the leaflets must be sutured to cloth-coveredstents in order to hold the leaflets in position for proper opening andclosing of the valve. A recent advance has been made in this regard byusing “stentless” porcine valves that are sutured directly to thepatient's native tissues for aortic valve replacement, but the problemof chemical fixation remains. In addition, these stentless artificialvalves cannot be used for mitral or tricuspid valve replacement.

[0034] Perhaps the major limitation of the “Function Follows Form”concept is that no efforts have been made previously to approximate theform of either the mitral valve or the tricuspid valve. If animal tissuevalves are used to replace either of these native valves, thetri-leaflet porcine aortic valve prosthesis or the tri-leaflet bovinepericardial valve prosthesis is normally used. In doing so, even thefaulty concept of “Function Follows Form” is ignored, since there are noartificial valves available for human use that approximate the anatomy(form) of the native mitral or tricuspid valves.

[0035] The nearest attempt at reproducing the function of the nativemitral valve was reported by Mickleborough et al in 1989. These testsinvolved the use of commercially-prepared sheets of pericardial tissuefrom cows, which had been treated with glutaraldehyde before storage andshipping. A longitudinal suture line was used to convert the flat sheetof tissue into a cylinder, then two triangular regions were removed fromone end of the cylinder, to generate two flaps. The inlet end wassutured to the mitral valve annulus, while the two tissue flaps at thecarved outlet end were sutured to the papillary muscles.

[0036] The mitral valve disclosed by Mickleborough et al suffers from adrawback which is believed to be important and perhaps even crucial toproper valve functioning. In a properly functioning natural valve, theanterior leaflet does not have its center portion directly attached tothe anterior papillary muscle via chordae. Instead, the anterior leafletis attached to both the anterior and posterior papillary muscles, viachordae that are predominantly attached to the peripheral edges of theleaflet. In the same manner, a native posterior leaflet is attached toboth the anterior and posterior papillary muscles, via chordae that arepredominantly attached to the peripheral edges of the leaflet. As aresult, the line of commissure (closure) between the two mitral leafletswhen the valve is closed during systole is oriented in roughly the samedirection as an imaginary line that crosses the tips of both papillarymuscles. This orientation of the leaflets and papillary muscles is shownin illustrations such as page 11 of Netter 1969. This naturalorientation can be achieved in the valve of the subject invention asdepicted in FIGS. 2 and 3, discussed below.

[0037] By contrast, the replacement valve described by Mickleborough etal alters and distorts the proper orientation of the replacementleaflets. Mickleborough's approach requires each sculpted leaflet to betrimmed in away that forms an extended flap, which becomes a relativelynarrow strand of tissue near its tip. The tip of each pericardial tissuestrand is sutured directly to a papillary muscle, causing the strand tomimic a chordae tendineae. Each strand extends from the center of aleaflet in the Mickleborough et al valve, and each strand is sutureddirectly to either an anterior and posterior papillary muscle. Thisrequires each leaflet to be positioned directly over a papillary muscle.This effectively rotates the leaflets of the Mickleborough valve about90° compared to the leaflets of a native valve. The line of commissurebetween the leaflets, when they are pressed together during systole,will bisect (at a perpendicular angle) an imaginary line that crossesthe peaks of the two papillary muscles, instead of lying roughly alongthat line as occurs in a native valve.

[0038] There has been no indication since the publication ofMickleborough et al 1989 that their approach is still being studied(either by them, or by any other research team), and there has been noother indication during the intervening years that their approach islikely to lead to a valve replacement technique for actual use inhumans.

[0039] It should be noted that one of the primary goals of Mickleboroughand her associates apparently was to propose a new way to maintaincontinuity between the valve annulus and the papillary muscles. It wasfirst proposed about 30 years ago (by C. W. Lillehei and perhaps byothers as well) that proper muscle tone of the left ventricular wall,and proper postoperative ventricular functioning, required atension-bearing connection between the mitral valve annulus and thepapillary muscles on the inside of the ventricular wall. This suggestionwas widely ignored in the design of replacement mitral valves, whichrequired excision of the chordae tendineae without making any effort toprovide a substitute that would keep the ventricular wall coupled to thevalve annulus. However, various studies (such as Rittenhouse et al 1978,David 1986, Hansen et al 1987, and Miki et al 1988) continued toindicate that the tension-conveying role of the chordae was important toproper ventricular function. Based on those studies, Mickleborough et alapparently were attempting to create and propose a new valve design thatcould accomplish that goal. They did indeed accomplish that goal, andthe apparent lack of any follow-up or commercialization of their designpresumably was due to other problems, such as the altered orientation ofthe leaflets in their design.

[0040] A different approach to creating artificial tissue valves isdescribed in articles such as Love and Love 1991, and in U.S. Pat. Nos.5,163,955 (Calvin et al 1992) and 4,470,157 (Love 1984). In thatresearch, surgeons harvested a piece of pericardial tissue from the sameanimal that was to receive the artificial valve. Such tissue, ifharvested from the same human body that will receive the implant, isreferred to as autologous or autogenous (the terms are usedinterchangeably, by different researchers). Using a cutting die, thepericardial tissue was cut into a carefully defined geometric shape,treated with glutaraldehyde, then clamped in a sandwich-fashion betweentwo stent components. This created a tri-leaflet valve that againresembles an aortic or pulnonary valve, having semilunar-type cuspsrather than atrioventricular-type leaflets. These valves were thentested in the mitral (or occasionally tricuspid) valve position, usingsheep.

[0041] Although those valves were structurally very different from thevalves of the subject invention, the Love and Love article is worthattention because it discusses chemical fixation. They usedglutaraldehyde treatment even though their tissue source was from thesame animal and was therefore non-antigenic, because earlier reports andtests had suggested that some types of untreated autologous tissuesuffer from thickening and/or shrinkage over time. Love and Lovesuggested that glutaraldehyde can help such tissue resist such changes,apparently by forming crosslinking bonds that tend to hold adjacentcollagen fibers in a fixed-but-flexible conformation. This use ofglutaraldehyde fixation as a treatment to reduce shrinkage or otherphysical distortion (as distinct from using it as a method of reducingtissue antigenicity) is an old and well-established technique fortreating non-autologous tissue, but whether it is also beneficial fortreating autologous tissue has not yet been extensively evaluated. Theeffects of chemical fixation of intestinal or other tubular tissue usedto create heart valves as described herein can be evaluated by routineexperimentation.

[0042] Another report describing the use of autologous tissue toreconstruct mitral valves is Bailey et al 1970. However, Bailey et alfocused on repairing rather than replacing mitral valves, usually bycutting an incision into one or both leaflets and then inserting asegment of tissue into the incision to enlarge the leaflet(s).

Physiologic Factors and in Utero Development

[0043] The subject invention relates to a method of using tubularstarting material to replace any of the four heart valves during cardiacsurgery. This approach is supported by and consistent with a fundamentalprinciple of native heart valve function, which either went unrecognizedin previous efforts to develop replacement valves, or which wassacrificed and lost when compromises were required to adapt availablematerials to surgical requirements.

[0044] The basic principle, which deserves repeated emphasis because ithas been so widely disregarded by other efforts in this field, is thatForm Follows Function. In one manifestation of this principle, if anartificial valve can be created that can truly function like a nativevalve, its resultant form will be similar to that of the native valve.

[0045] A highly important observation by the Applicant that contributedto the recognition of the pervasive and overriding importance of thisprinciple was the following: the entire cardiovascular system, includingthe heart, begins in utero as a single, relatively straight tube oftissue. Anatomical drawings depicting the in utero development of theheart are available in numerous scientific publications and books,including Netter 1969. As shown in those figures (or similar figuresavailable in other medical reference works), the so-called “heart tube”is readily discernible by the 23rd day of gestation. This tube willeventually develop into the entire cardiovascular system of the body.The tissue that exists between the portion of the tube destined tobecome the ventricles, and the portion that will become the atria, iswhere the mitral and tricuspid valves will ultimately form. This regionof tissue is in a tubular form.

[0046] The heart tube undergoes a process of convolution beginning atapproximately 25 days gestation. This convolution of the heart tubeforms what is called the “heart loop” and is responsible for the aorticvalve ultimately coming to lie adjacent to the mitral valve. When amature mitral valve is viewed from the atrial side, the anterior portionof the mitral valve annulus is relatively flat. This distortion of theoriginal roundness of the mitral annulus is caused by the presence ofthe aorta against the anterior mitral valve. It is also the reason thatthe anterior leaflet of the mitral valve is contiguous with the aorticvalve annulus. Finally, it explains why accessory atrioventricularconnections (accessory pathways) that occur in the Wolff-Parkinson-Whitesyndrome never occur in this portion of the mitral valve annulus; thisis the only portion of the entire atrioventricular groove on either sideof the heart where the atrium and ventricle were never contiguous duringfetal development.

[0047] By approximately 56 days gestation, the heart tube developmentreaches a stage that displays a first constricted tube region betweenthe primordial right atrium and the primordial right ventricle (thisportion of the tube will become the tricuspid valve) and a secondconstricted tube region between the primordial left atrium andprimordial left ventricle (the future mitral valve).

[0048] As the developing heart of a fetus undergoes variousconvolutions, separations, and compartmentalizations, the tissues thatare to eventually become the heart valves maintain their tubularstructure. Prior to the onset of fetal heart function, portions of thewalls of these tubular structures undergo a process of dissolution,leaving behind only those portions of the original tubes that arenecessary for the proper functioning of the heart. This dissolution alsoaffects the ventricular walls as they rapidly enlarge in size; if it didnot, the walls would become prohibitively thick as the physical size ofthe heart increased, and the heart could not function effectively as apump since it would become simply a large mass of ventricular muscle.

[0049] The dissolution process also operates on the tubularconstrictions that will become the four heart valves. In the case of thesemilunar valves (the aortic and pulmonary valves), the necessaryfunctional remnants are the three cusps, which are the remains of thefunctioning portion of a simple tube. This principle is strengthened bythe fact that although frequent reference is made to the pulmonic oraortic valve “annulus”, knowledgeable anatomists are quick to point outthat there is no such anatomical structure. The thickened tissue that iscommonly referred to as the “annulus” of these valves is simply theflexion point of the three cusps, the remnants of a simple tube that isfixed at three points distally and subjected to uniform pressure on itsoutside, resulting in collapse of the tube on the three sides betweenthe points of distal fixation, which in turn, results in three nearlyidentical cusps. All tissue other than these moveable and functionalcusps has undergone the normal process of dissolution as the aorta andpulmonary artery have enlarged, leaving behind only that tissuerecognized as the cusps of these semilunar valves.

[0050] At the mitral and tricuspid valves locations, the dissolutionprocess leaves behind the valve leaflets, chordae tendineae, andpapillary muscles in both the right ventricle (tricuspid valve) and leftventricle (mitral valve). In other words, that portion of the originaltube that is necessary for the development of the native heart valves isspared the dissolution process and the rest of the tube dissolves away.The valve leaflets are tube remnants, which are attachedcircumferentially to the fibrous annulus of the heart at their base andattached by chordae tendineae (additional tube remnants) at their freeedges to papillary muscles (still more tube remnants) inside theventricles. The leaflets, chordae tendineae, and papillary muscles ofeach the two A-V valves represent the necessary functional remnants ofthe original in utero tubular structures of the heart.

[0051] Using “Form Follows Function” as a basic guiding principle, thepresent invention is based on the realization that a tubular structurehaving proper size and suitable material characteristics, if placedinside a mitral or tricuspid valve annulus after excision of the nativevalve (or inside an aorta or pulmonary artery, as described below) willfunction exactly like the normal valve in that position, assuming properfixation of the inlet and outlet ends of the tube. The “Form FollowsFunction” principle predicts that if the intended function of areplacement valve is to emulate the performance and function of a nativemitral or tricuspid valve, then the form of a replacement valve—thestructure and appearance of the replacement valve—should resemble theform of a native mitral or tricuspid valve. Since the native valves aregenerated from tubular starting material during fetal development, thisprinciple further suggests that replacement valves should also begenerated from tubular material.

[0052] This principle is given added support by the results that wereobserved in an artificial tissue valve that had been implanted into themitral valve position in a human heart. The Applicant learned of theseresults during a presentation by Professor Donald Ross of the NationalHeart Hospital and Brompton Hospital (London, England), the cardiacsurgeon who had performed that surgery. The implanted valve wasoriginally a commercially available trileaflet tissue valve that wasimplanted into the mitral position in a 35-year-old female. Thetrileaflet valve had been constructed using fascia late tissue (arelatively tough and flexible layer of tissue that normally surroundscertain types of muscles) which had been sewn into a circular stent.After 5 years, the artificial valve had to be removed because itsleaflets had become calcified and immobile, resulting in both mitralstenosis and mitral insufficiency. Upon exposing the artificial valveduring the removal surgery, the surgeon was struck by the similarity inshape and appearance of the diseased trileaflet valve to a normal mitralvalve. The commissures of the three leaflet artificial tissue valve hadfused in a manner so that two leaflets had been formed: one largeanterior leaflet, and one smaller posterior leaflet, as seen in a nativemitral valve. Furthermore, the commissure between the two leaflets whenthe patient's valve was closed by back pressure closely resembled thesemi-circular commissure formed by leaflets in a native mitral valve.

[0053] During the presentation by Professor Ross, the Applicantwitnessed a picture showing how the three-leaflet artificial valve hadbeen converted into a bi-leaflet valve during the course of five yearsinside a human heart. It became clear to the Applicant that thepatient's heart had been attempting to make the valve conform to theheart's functional needs.

[0054] Prior to witnessing that presentation, the Applicant had alreadybeen considering the question of whether tubular tissue might be usefulfor creating replacement heart valves. After seeing Prof. Ross'sphotographs, which provided strong physiological confirmation of the“Form Follows Function” principle, the Applicant began to carry outexperiments to assess the possibility of using tubular tissue to replaceheart valves. In a simple mechanical test, he obtained some highlyflexible rubber tubes by cutting off the fingers of surgical gloves,then he sculpted the finger tubes to resemble the leaflets of mitral ortricuspid valves, then he sutured the sculpted rubber tubes inside ofslightly larger tubes made of Dacron™. An internal rubber tube wassecured proximally around the entire periphery of a tube, to emulate avalve annulus, and the sculpted rubber flaps at the distal ends werecoupled to the tube walls by means of loose suture strands that emulatedchordae tendineae. When cyclical pressure was generated by attempting toblow and then suck air through the tube, the interior rubber leafletsopened and closed in a manner that looked identical to natural mitral ortricuspid leaflets opening and closing. This provided additionalconfirmation of the “Form Follows Function” principle.

[0055] The physiologic principle that the functional components ofnative heart valves are the remnants of simple tissue tubes, and theidea of using tubular structures to replace defective heart valves; hasbeen completely ignored in the design and construction of allreplacement valves in use today. Indeed, although “Form FollowsFunction” is a well-respected principle in fields such as engineering orevolutionary studies, it is often disregarded among medical researchers,some of whom apparently seem to feel that efforts to sever or reversethis relationship represent triumphs of technology over nature. As anexample, kidney dialysis machines, which look nothing like normalkidneys, are a purely technological, non-natural solution; they use acompletely artificial form to generate and provide a certain neededfunction. However, as any dialysis patient would attest, they fall farshort of being truly optimal.

[0056] In a similar manner, all artificial heart valves in use today,whether tissue or mechanical, have been designed based on the beliefthat either: 1) function can be forced to follow form (aortic andpulmonary valve replacement), or 2) neither function nor form of thenative valve can be reproduced, so a replacement valve (either tissue ormechanical) must merely function as a one-way passive valve (mitral andtricuspid valve replacement). In the case of artificial tissue valves,the form of an artificial valve is established first, in the hope thatthe valve will function in a manner similar to a native valve. In thecase of artificial mechanical valves, the disruption of the interactionbetween form and function goes even farther, and the caged balls, hingedflappers, and other devices in mechanical valves have even less physicalsimilarity to native valves. However, the problems in both of theseapproaches are evident in the limitations suffered by every type ofreplacement valve that is in use today.

[0057] There is another way to express the concept of “Form FollowsFunction” which may help explain it to people who would point tomechanical heart valves, dialysis machines, and other non-natural formsthat have been used to mimic the function of body parts. In suchexamples, function is forced to follow form. In crude and simple terms,the function of a heart valve is merely to allow flow in one directiononly. Any type of mechanical check valve with a caged-ball orflapper-and-seat design can provide that level of function.

[0058] However, when the long-term aspects of heart valve function arealso taken into account (including the functions of providing lowhemolysis, low turbulence, avoiding calcification, etc.), it becomesclear that artificial forms cannot fully provide those functions. Thebest and perhaps only way to provide a replacement valve with thecomplete, long-term functionality of a natural heart valve is by givingproper deference to the relationship between function and form.

[0059] This principle can be stated as, “Form and function form acycle.” Each follows the other, but each also precedes and affects theother. If either half of this cycle is violated or disrupted, it willcreate problems that will stand in the way of an optimally functional,reliable, durable system with minimal hemolysis, turbulence, andcalcification. On a short-term basis, function can be forced to adapt toan unnatural form; however, any such short-term solution will be plaguedby problems and limitations over the long run. The problems andshortcomings of current mechanical replacement valves are a clear anddirect demonstration of this principle.

[0060] The following series can help to illustrate the principle, “Formand function form a cycle.” First, a form is created: tubular tissue isused to create a new mitral valve. This form then creates a function:the new valve allows flow in only one direction, from the atrium to theventricle. This function, in turn, creates another form: the leaflets ofthe new mitral valve will close in a “smile” configuration resembling anative mitral valve during closure. This secondary form then creates asecondary function: the new valve will provide good long-term use andlow levels of turbulence, hemolysis, calcification, and leaflet stress.Form and function form a cycle, and this cycle cannot be disrupted byinjecting and imposing an artificial, unnatural form in the heartwithout impeding the ability of proper form and proper function tointeract with, support, and enhance each other.

[0061] In addition, certain items of evidence suggest that conventionalreplacement tissue valves, which cause high levels of turbulence,contribute to the important problem of leaflet calcification. Thecorrelation between high turbulence and leaflet calcification isdiscussed below.

OBJECTS OF THE INVENTION

[0062] On the basis of the physiological facts, observations, andprinciples described above, and on the basis of experiments carried outby the Applicant, it appears that if heart valves are damaged ordiseased to the point of requiring replacement, they should be replacedby tubular structures which function like native heart valves.

[0063] Accordingly, one object of this invention is to provide areplacement heart valve including a tubular segment of material thatmore closely resembles the construction and function of a native heartvalve.

[0064] This and other objects and advantages of the invention willbecome clear as the invention and certain preferred embodiments aredescribed below and in the drawings.

SUMMARY OF THE INVENTION

[0065] In accordance with one aspect of the present invention, aprosthetic heart valve comprises at least two cusps comprised of a thinand flexible material. Each cusp has an inner surface and an outersurface and is attached to another cusp along a longitudinal sutureline. Each of the cusps is adapted to flex inwardly into and out ofengagement with another cusp so as to close and open the valve inresponse to force by blood pressure. A portion of the inner surface ofone cusp is in a facing relationship with a portion of the inner surfaceof another cusp adjacent the longitudinal suture line when the valve isopen.

[0066] In accordance with another aspect, the present inventiondiscloses a method for making a prosthetic heart valve. A section ofsubstantially flat, flexible material is provided, and at least twoleaflets are cut out of the flat material. Each of the leaflets has aninner face, an outer face, an in-flow end, an out-flow end, and sideedges. The side edges of adjacent leaflets are sewn together so as toform a substantially tubular valve structure having an in-flow end andan out-flow end. Each leaflet is configured so that a portion of theinner face of each leaflet is in a facing relationship with a portion ofthe inner face of an adjacent leaflet.

BRIEF DESCRIPTION OF THE DRAWINGS

[0067]FIG. 1 is a cutaway depiction showing the mitral valve on the left(systemic) side of the heart and the tricuspid valve on the right(pulmonary) side of the heart, showing a tubular segment adjacent to theheart, having a size and configuration that will render the segmentsuitable for implantation as a replacement mitral valve.

[0068]FIG. 2 depicts a top view (from the left atrium) of a tubulartissue valve sutured into the mitral position, showing the orientationof the anterior and posterior leaflets in relation to the anterior andposterior papillary muscles.

[0069]FIG. 3 shows a top view of the tubular mitral valve duringsystolic contraction of the ventricle. The two leaflets are pressedagainst each other in a natural “smile” configuration; this closure(approximation) of the leaflets prevents blood from flowing back intothe atrium.

[0070]FIG. 4 depicts a tubular segment that has been inserted into anaorta or pulmonary artery, to create a semilunar valve with cusps.

[0071]FIG. 5 depicts a semilunar valve as described herein, in a closedposition.

[0072]FIG. 6 depicts a configuration that can be used if desired tosecure tubular tissue inside an aorta in a configuration in which thecusps of the valve are pinched together adjacent to the arterial wall.

[0073]FIG. 7 depicts a tubular segment of intestinal or syntheticmaterial, enclosed within a sealed pouch that maintains sterility of thetubular segment.

[0074]FIG. 8 depicts a tubular tissue segment of intestinal or syntheticmaterial which has been attached to an annuloplasty ring, enclosedwithin a sealed sterile pouch.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENT

[0075] This invention comprises a method of using tubular material, suchas a tubular segment of synthetic material, or a segment of smallintestinal submucosal (SIS) tissue, to replace heart valves (i.e.,aortic or pulmonary valves) during cardiac surgery.

[0076] As used herein, “tubular starting material” refers to materialthat is harvested from a human or animal body in tubular form (such asintestinal tissue), and to synthetic material that is synthesized,molded, woven, or otherwise created in tubular form. Tubular startingmaterial is distinct from flat material that has been secured by meanssuch as longitudinal suturing, into tubular form.

[0077] This approach to using tubular material is substantiallydifferent from all artificial valves (mechanical or tissue) that areavailable for human use today. It is based upon the recognition of afundamental principle of native heart valve structure and function,which either has gone unrecognized or which has been sacrificed and lostwhen compromises were required to adapt available materials to surgicalrequirements. The basic principle, as described in the Backgroundsection, is that “Form Follows Function.” If an artificial valve can becreated that truly functions like a native valve, its resultant formwill, of necessity, be similar to that of a native valve.

[0078] To assess and display the “Form Follows Function” principlemathematically, a flexible tubular segment was created in athree-dimensional CAD-CAM program, which was run on a computer in theApplicants research laboratory. The tube segment was affixed, at certaindesignated points, to the interior wall of a cylindrical flow conduit.One end (corresponding to the inlet) of the flow conduit and flexibletube were flattened on one side, and the flexible tube inlet was fixedaround the entire inner circumference of the flow conduit. The other end(the “outlet”) of the flexible tube was fixed at only two opposed pointsinside the flow conduit. An external force of 120 mm Hg (correspondingto the pressure generated in the left ventricle during systoliccontraction of the ventricle) was applied to the outlet end of theflexible tube, and all unattached areas of the flexible tube wereallowed to flex and move according to the mathematical deformations andconstraints that occurred as a result of the imposed conditions. Theprogram used an iterative finite-element algorithm to determine whereeach square in an imaginary grid on the surface of the flexible tubewould be located. It was allowed to run to completion, which tookapproximately 12 hours. At the end of these calculations, the wall ofthe tube was visually depicted by the computer,, and the resultant shapeof the tube perfectly resembled the shape of a mitral valve when closedby back-pressure in a left ventricle.

[0079] A similar CAD-CAM analysis was performed for an aortic (orpulmonary) valve in which the inlet end of the flexible tube was fixedcircumferentially around the inlet of the flow conduit, and the otherend of the flexible tube was fixed at 3 equidistant points around thecircumference of the conduit. The external pressure applied to theoutside of the tube was 80 mm Hg, corresponding to the arterial pressureexerted on normal aortic valve leaflets during diastole. Again, theresultant shape of the tube after 12 hours of mathematical deformationappeared to exactly mimic a natural aortic valve.

[0080] Until the CAD-CAM studies had been performed, the relationship ofthe principle of “Form follows Function” to the form and function ofnative human heart valves was only a hypothesis. However, the fact thatthe simple tubes, faxed in a known anatomic manner, were deformed byphysiologic pressures into a shape that exactly mimicked the shape ofnative heart valves confirmed two aspects of the hypothesis in aconvincing manner: 1) native heart valves do in fact function like thesides of compressed tubes when they close, and 2) the engineeringprinciple of Form Following Function is applicable to native human heartvalves.

[0081] To the best of the Applicant's knowledge, the significance of thein utero development of native heart valves as the remnants of simpletissue tubes, and the principle of using tubular structures to replacedefective heart valves in an effort to reproduce the function of thenative valves, has not previously been recognized or disclosed. The mostclosely related effort at creating artificial heart valves weredescribed in Mickleborough et al 1989, which was discussed in theBackground section. However, they did not use tubular material as thestarting material; instead, they used bovine pericardial material, whichis effectively flat. That approach required the used of animal tissuethat had been treated with chemicals (glutaraldehyde) to reduce itsantigenicity.

[0082] The approach described in Mickleborough et al 1989 also requiredthe creation of a suture line to convert the flat pericardial tissueinto a quasi-tubular structure. This created certain problems and risks,since a longitudinal suture line requires additional handling of thepericardial material by surgeons. This additional handling would need tobe done after the patient's chest and heart have been surgically opened,therefore increasing the time during which the patient needs to be kepton cardiopulmonary bypass (CPB). As is well known; any increase in thelength of time of artificial circulatory support is adverse, and anyreduction of the time required for keeping a patient on CPB isbeneficial. In addition, the creation of a longitudinal suture lineduring a mitral or tricuspid valve replacement might increase the riskof tearing the leaflet material at the suture points, and the risk ofthrombosis. For both of these reasons, the use of tubular startingmaterial (such as intestinal tissue) as described herein, rather thanflat starting material, is advantageous, provided that the intestinaltissue segment has a diameter compatible with the valve being created.As discussed below, if the diameter of a patient's autologous intestinalsegment is not compatible with the diameter of the annulus of a heartvalve being replaced (which is likely when aortic or pulmonary valvesare being replaced), a pre-treated packaged segment of SIS tissue havingthe desired diameter from an animal (such as a pig) or a human cadavercan be used to avoid the need for using a longitudinal suture line toconvert flat material into tubular material.

[0083] In comparing the subject invention to the prior art ofMickleborough et al, it should also be kept in mind that the approachused by Mickleborough et al caused the anterior and posterior leafletsof their replacement valve to be rotated roughly 90° compared to thenative leaflets in a native mitral valve. By contrast, the subjectinvention allows the creation of mitral leaflets having a naturalorientation. This factor was discussed in the Background section and isdepicted in FIGS. 2 and 3.

Use of Intestinal Tissue

[0084] The harvesting, preparation, and use of intestinal tissue, forcreating replacement heart valves, is described in detail in the twoabove-cited parent applications (Ser. Nos. 08/146,938, now U.S. Pat. No.5,480,424, and 08/459,979, now U.S. Pat. No. 5,713,950), which areincorporated by reference in their entirety. The following discussionregarding implantation of intestinal tissue which has been properlyharvested and prepared also applies directly to implantation ofsynthetic and any other material.

Methods of Implantation

[0085] The SIS tissue segment can be implanted in a mitral valveposition using any of several methods. In one method, it can beinitially implanted as an unsculpted tube, then trimmed as necessary topreclude redundancy of the leaflets. This method can be performed asfollows. The patient or animal is placed on total cardiopulmonary bypassso that the heart can opened safely. The heart is either arrested orfibrillated and the mitral valve is exposed through an incision in theleft atrium. The leaflets and chordae tendineae of the native mitralvalve are surgically removed, leaving behind a mitral valve annulus 121.This annulus 121 has a roughly circular shape; however, as shown in FIG.2, there is a somewhat “flattened” area 123 in the annulus, on the sideclosest to the aortic valve. In an intact native mitral valve, the baseof the anterior leaflet is attached to this “flattened” region of themitral valve annulus. The inlet (proximal) 202 end of the tubularsegment 200 is sutured into the mitral valve annulus 121, using a sutureline 204 which travels around the entire circumference of the annulus121 and the tubular segment 200. If desired, an annuloplasty ring (suchas illustrated in FIG. 8) can be used to create a bridge between thevalve annulus 121 and the SIS tissue inlet 202.

[0086] After the annulus has been properly secured, the length of theSIS segment can be trimmed to eliminate most of the excess length whileretaining adequate tissue for the surgeon to work with. Sutures are thenused to temporarily secure the outlet (distal) end of the tube to thepapillary muscles at a distance from the mitral annulus compatible withthe desired degree of “closure” of the tubular valve. This can be doneby placing a tacking suture through the appropriate side of the tubedistally and then passing it through the tip of the anterior papillarymuscle 126. The same procedure is performed on the opposite side of thetube, temporarily attaching it to the posterior papillary muscle 128.

[0087] Saline is then injected into the left ventricular chamber 112,which will remain capable of sustaining fluid pressure inside a closedchamber if access to the mitral valve is obtained via an incisionthrough the left atrial wall. The saline flush generates fluid pressurein ventricle 112, which causes the sides of the tube to be forced intoapproximation. In other words, the saline flush closes the newly-createdvalve.

[0088] Once the proper site of attachment of the distal end of the tube200 to the two papillary muscles 126 and 128 has been determined, thetube 200 can be permanently attached to the tips of the papillarymuscles 126 and 128. This can be done in any of several ways. If thedistal end of the SIS tissue has been carved, trimmed, or sculpted tocreate elongated wedges or strands of tissue which will serve assubstitute chordae tendineae for attachment purposes, the distal ends ofthe sculpted tissue segments can be sutured to the papillary muscles. Ifdesired, the tips of the tissue segments can be inserted into smallincisions in the tips of the papillary muscles; these can then bereinforced using reinforcing devices on the outsides of papillarymuscles, to reduce the risk of tearing the tissue segments or the tipsof the papillary muscles.

[0089] Alternately, preliminary tests on animals indicate that inanimals which have normal papillary muscles of sufficient length, thedistal end of the SIS tube does not need to be trimmed to createelongated wedges or strands of tissue for attachment purposes. If theblunt end of an SIS tube is sutured to the anterior and posteriorpapillary muscles, this will effectively create anterior and posteriorleaflets that will emulate native leaflets after the heart startsbeating again. Even if no tissue between the two leaflets is removed, itappears that a sufficiently large flow channel can be provided betweenthe papillary muscles to handle the necessary flow.

[0090] Accordingly, it does not appear to be essential to remove suchtissue by a sculpting or trimming procedure. Nevertheless, a sculptingor trimming step that physically divides the replacement leaflets intoan anterior leaflet that has been partially divided from the posteriorleaflet is presumed to be preferable, because it can help the valveleaflets more closely emulate the physical shape of the leaflets in anative mitral valve. If such a sculpting or trimming step is desired, itcan be carried out at any suitable time during the operation, such asimmediately after a temporary suturing step followed by a saline flushhave confirmed that a certain attachment configuration will function inthe desired manner.

[0091] After the SIS tissue has been permanently sutured to thepapillary muscles, and after any trimming or sculpting step has beencompleted, the left atrium is closed and the heart is restarted. Duringeach heartbeat, as blood crosses the valve in a forward direction,because of diastolic expansion of the ventricular chamber andcontraction of the left atrium, the leaflets will be forced open.

[0092] It should be noted that this tubular valve, when open during thesystolic phase of each heartbeat, has no obstructions in its flow path.By contrast, in every type of artificial mechanical valve being usedtoday, various devices must be positioned in the flow path of the blood.These hinder blood flow, leading to pressure gradients across the valve,especially at high flow rates and with small sized valves, and they alsogenerate turbulence that can damage blood cells. Moreover, sinceprevious artificial tissue valves require stents and do not mimic thefunction of native valves; they also cause turbulence in blood flow, animportant factor in the production of calcification in the leaflets ofthe artificial tissue valve.

[0093] As soon as ventricular expansion is complete and systoliccontraction of the ventricle begins, the pressure generated inside theventricle will press the two sides of the tube 200 against each other,closing the valve and forcing the blood to exit the ventricle throughthe aortic valve in the normal and proper manner. FIG. 3 shows a topview (from the left atrium) of the closed valve during contraction ofthe ventricle. The two sides of the tube effectively create a newanterior leaflet 122A and a new posterior leaflet 124A, which closelyemulate the shapes and orientations of the native anterior leaflet 122and the native posterior leaflet 124. Closure (approximation) of thereplacement leaflets 122A and 124A against each other, caused by thepressure of the blood inside the ventricle, prevents backflow of blood(regurgitation) back into the left atrium.

[0094] In a native mitral valve, the commissure between the two naturalleaflets is curved, in a manner that resembles a smile. This occursbecause: 1) the mitral valve annulus 121 is not completely round, andhas a “flattened” region 123 on the side closest to the aortic valve,and 2) pressure on the outside of any tube that has one flat side and isattached at two points distally (in line with the two ends of the flatside) will result in apposition of the two sides of that tube in amanner that resembles a smile. In a simple tube, this results in theside of the tube that is flattened occupying the majority of theorifice. In the case of the mitral valve, it results in the anteriorleaflet being larger than the posterior leaflet, thereby occupying themajority of the valve orifice in the closed position. As shown in FIG.3, this same type of “smile” commissure between the two leaflets iscreated by proper insertion and attachment of the replacement valve.

[0095] In some situations, it may be necessary to resect a small portionof the distal anterior wall of the SIS tube to prevent “systolicanterior motion” of the new anterior leaflet during systolic contractionof the ventricle. The phenomenon of systolic anterior motion of theanterior leaflet, which can lead to interference of blood flow throughthe aortic valve, is part of the etiology of a certain condition calledHypertrophic Obstructive Cardiomyopathy (HOCM), which affects somepatients, and it must be avoided in patients who are likely to besubject to such a condition.

Tricuspid Valve Replacement

[0096] Tricuspid valve replacement in humans is especially problematicbecause tissue valves tend to fail earlier and mechanical valves tend toform clots at a much higher rate than either do in the mitral or aorticposition. In addition, when tricuspid valves require replacement forinfection, re-infection of the new artificial valve is so common thatsome authors have actually advocated removal of an infected native valvewithout replacement with a new artificial one! Thus, the need for asatisfactory artificial valve for tricuspid valve replacement isespecially acute.

[0097] Tricuspid valve replacement can be created in essentially thesame manner as mitral valve replacement, described above. Preliminarystudies on animals indicate that the natural shape of the tricuspidannulus at the proximal end of a tube valve and three points of fixationdistally to the normal papillary muscles in the right ventricle willresult in an anatomically correct trileaflet tricuspid valve. However,it should be recognized that in the right ventricle, papillary musclesare more variable and unpredictable in their placement than in the leftventricle; accordingly, tricuspid valves tend to be more difficult toreplace than any of the other three valves, and successful replacementdepends even more heavily upon the experience and expertise of thesurgeon in tricuspid valve repair than in other valves.

Optional use of an Annuloplasty Ring for Replacement ofAtrio-Ventricular Heart Valves

[0098] A preferred mode for surgical insertion of the valves describedherein completely avoids the use of an annuloplasty ring. As foreignobjects that come into direct contact with blood (and which typicallyhave rough surfaces, to facilitate sewing), annuloplasty rings in themitral or tricuspid position pose a theoretical problem in regard to thethreat of thrombosis. Accordingly, by disclosing replacement valves thatcan be created without using annuloplasty rings, this invention offersan advance over prior art replacement valves currently in use.

[0099] However, clinical practice has shown that any potential increasein the threat of thrombosis due to an annuloplasty ring in a mitral ortricuspid valve repair is moderately low; by way of illustration,surgeons often conclude that the increased risk of spontaneoushemorrhage associated with systemic anticoagulation outweighs the riskof thrombosis resulting from the use of annuloplasty rings. Accordingly,annuloplasty rings are widely used without severe adverse effects, andin many patients suffering from heart disease or congenitalabnormalities, they can be advantageous or even necessary.

[0100] Therefore, this invention discloses (1) replacement valves madeof tubular tissue (or suitable synthetic material) coupled toannuloplasty rings, and (2) a method of surgically implanting suchreplacement valves. In such cases, the tubular tissue will work in thesame manner as described above, while the annuloplasty ring will helpcreate a bridge between the inlet end of the tubular tissue segment, anda valve annulus in a patient (such as a patient whose native mitralvalve annulus is weak, dilated, and/or “rounded” out of its normalshape). The implantation of the annuloplasty ring can be carried outusing the same techniques that are currently used for mitral andtricuspid valve reparative techniques. After a segment of SIS tissue hasbeen harvested from the body of the patient receiving the heart valve,the inlet rim of the SIS tissue is sutured to an annuloplasty ring.After the annuloplasty ring has been sutured to an atrioventricularvalve annulus, the distal end of the SIS tissue is sutured to thepapillary muscles as described above.

[0101] Alternatively, if synthetic material or an SIS tissue segmentfrom an animal or human cadaver is used, the annuloplasty ring can becoupled to the tube and both can be packaged together in a sealedpackage which maintains their sterility. This article of manufacture isdescribed in more detail below and is shown in FIG. 8, in which atubular segment 500 has been attached to annuloplasty ring 502.Accordingly, the subject invention discloses a method of using smallintestinal submucosal (SIS) tissue in conjunction with an annuloplastyring to create a heart valve replacement.

[0102] It should be noted that the tubular valves of this invention donot require stents. As used herein, the term “stent” includes anyman-made device (other than a suture, annuloplasty ring, or leafletmaterial) which is surgically implanted in a patient's heart (or aortaor pulmonary artery) as part of a replacement valve, and which iscontacted by blood which flows through the heart (or aorta or pulmonaryartery). Stents are major components in all mechanical replacementvalves, since they must securely hold the ball, flapper, or othermovable elements of the valve in proper position; they are also used innearly every type of artificial tissue valve, to secure the tissue flapsin the proper configuration. The term “stent” does not includereinforcing pledgets placed on the outside of an aorta or pulmonaryartery, since such pledgets would not be contacted by blood flowingthrough the artery.

[0103] Stents are known to increase turbulence and thrombosis. Since thevalves disclosed herein are stentless, this invention offers animportant advance over prior art replacement valves which are currentlyapproved by the FDA.

[0104] In summary, the steps for creating an atrioventricular (mitral ortricuspid) replacement valve can be described as follows:

[0105] 1. A tubular segment is obtained, consisting of thin and flexibletubular tissue or synthetic material, having an inlet end and an outletend.

[0106] 2. The damaged or deformed leaflets of the native diseased valveare surgically removed from the heart of the patient, to generate anopen valve annulus. The chordae tendineae are also removed, while thepapillary muscles in the ventricular chamber are left intact.

[0107] 3. The inlet end of the tube is sutured to the valve annulus, orto an annuloplasty ring if necessary for a specific patient.

[0108] 4. The outlet end of the tube is sutured to the papillarymuscles, in a manner which will allow the outlet flaps to function asvalve leaflets that will open during ventricular diastole, when bloodflows from the atrium into the ventricle. The valve leaflets willapproximate and close the valve during ventricular systole, to preventbackflow when fluid pressure in the ventricle exceeds fluid pressure inthe atrium. The specific sites of attachment of the tubular material tothe papillary muscles should allow the resulting leaflets to approximatein a manner that emulates the shape and angular orientation of theleaflets in a properly functioning native valve.

Aortic (and Pulmonic) Valve Replacement

[0109] In a preferred method of creating a replacement for a semilunarvalve (i.e., an aortic or pulmonary valve), a segment of intestinaltissue several inches long is removed from the patient and treated toremove the serosa, smooth muscle, and mucosal layers in the same mannerdescribed above. This leaves a tubular structure made of the basementmembrane and submucosal layers, referred to herein as small intestinalsubmucosal (SIS) tissue. Alternately, as with atrioventricular tubularvalves, the tubular material may be obtained from other animals or fromhuman cadavers, or it may be manufactured from a suitable syntheticmaterial. For convenience, the discussion below will assume that an SISsegment is used. The desired length can range from about 2 cm forneonates to about 6 cm for adults.

[0110] To secure a tubular segment 200 inside an aorta in accordancewith one method (the same approach can be is used to create a pulmonicvalve in a pulmonary artery), an aortic wall is opened by an incisionabove the level of the commissural posts of the aortic valve, and thecusps of the native aortic valve are removed, leaving behind a valveannulus. The tubular SIS segment 200 is then inserted, and as shown inFIGS. 4 and 5, the tubular segment 200 includes an apparatus forattaching the inlet end to the interior surface of the aortic wall 250.The apparatus for attaching the inlet end comprises an inlet attachmentportion 203 on the tubular segment 200 that extends around thecircumference of the tubular segment. The inlet attachment portion 203on the tubular segment 200 is secured to the interior surface of theaortic wall 250 by a circumferential suture line 210. This step canutilize an annuloplasty ring if desired. The tubular SIS segment 200also includes an apparatus for attaching the outlet end of the tubularsegment directly to the interior surface of the aortic wall 250. Theapparatus for attaching the outlet end comprises first 223, second 224,and third 225 attachment points on the tubular segment 200. Eachattachment point is secured to the aortic wall 250 by attaching sutures200, including first 226, second 227 and third 228 attaching sutures. Inone preferred embodiment shown in FIG. 4, the attaching sutures 220 areshown to comprise three longitudinal suture lines 220 spaced atone-third intervals (120° apart from each other) around the internalperiphery of the aortic wall 250.

[0111] Suturing the tissue segment 200 to the inside of the aortic (orpulmonary artery) wall 250 by the three longitudinal suture lines formsan arrangement for opening and closing the outlet end 204 of the tubularsegment. The arrangement for opening and closing the outlet end of thetubular segment includes three flexible tissue regions 222, namely first230, second 231 and third 232 flexible tissue regions. The flexibletissue regions 230, 231, 232 function as respective first 233, second234 and third 235 valve cusps during operation of the valve, as shown inFIG. 5. After the tissue segment 200 is properly secured and thepatient's heart is closed by the surgeons and restarted, the three valvecusps 233-235 will go through a cyclical movement with each heartbeat.During the systolic stage (ventricular contraction) of each heartbeat,depicted in FIG. 4, the cusps 222 be held in an open position by bloodentering the inlet end 202 and exiting the outlet end 204. When thesystolic stage ends and the left ventricle begins to expand duringdiastole, back pressure in the aorta (or pulmonary artery) causes thethree valve cusps 233-235 to flex in a downward and inward direction.However, the cusps are constrained and their motion is limited by theattaching sutures 220. The combination of pressure and tension causesthe three valve cusps 233-235 to flex inwardly, as shown in FIG. 5,thereby forcing the valve into a closed position and preventing backflowinto the ventricle.

[0112] An alternative to placing the three parallel rows of suture linesinside the aorta (or pulmonary artery) as described above is to fix theoutlet end of the tube valve at three equidistant points (120° apartaround the circumference of the outlet end) only. This technique willpreclude the necessity for the longitudinal suture lines described abovebut will allow the valve to function in the same manner.

[0113] If desired, the three longitudinal suture lines 220 (or the threepoints of fixation of the outlet end of the tube) can be reinforced bystrips (often called pledgets) placed on the exterior of the aorticwall. These reinforcing strips can be made of autologous tissue,materials sold under trademarks such as TEFLON, GORETEX, SILASTIC, orany other suitable material. Since these strips would be positionedoutside the aorta or pulmonary artery, they would not come into contactwith blood flowing through the artery. Therefore, they can reinforce thearterial wall, distribute any tensile stresses more evenly across awider area of the arterial wall, and reduce the risk of tearing thearterial wall, without increasing the risk of thrombosis inside theartery. Depending on the positioning of the replacement valve in theaorta, it may also be desirable to place a similar strip around theexterior of an aorta or pulmonary artery to reinforce thecircumferential inlet suture.

[0114] If a need becomes apparent in a specific patient, similarreinforcing strips can also be positioned inside an aorta or pulmonaryartery, and a stent can be used to reinforce the inlet attachmentportion. However, any reinforcing component which is exposed to bloodinside the artery would increase the risk of thrombosis and probablywould suggest to the surgeon that the patient would need to be placed onanticoagulant drugs to reduce the risk of clot formation.

[0115] In some patients, it may be preferable to use an annuloplastyring for replacement of an aortic or pulmonary valve. Accordingly, thesubject invention discloses a method of replacing the aortic andpulmonary valves in which a round annuloplasty ring is used inconjunction with the artificial tubular tissue or mechanical valve.After obtaining a tubular segment of tissue or synthetic material, theinlet attachment portion of the tubular segment is sutured to a roundannuloplasty ring which is then sutured into the aorta (or pulmonaryartery) at the level of the lowest point of the excised native semilunarvalve. The distal end of the tubular segment for both aortic valves andpulmonary valves is then handled in the same manner as described abovefor these valves without annuloplasty rings.

[0116] Two additional variations in aortic and pulmonary replacementvalves have been recognized and will be evaluated if an apparent needarises. First, initial tests on dogs, coupled with computer analysisusing an iterative finite-element algorithm to calculate the stresses oneach portion of a cylindrical tissue segment constrained as describedherein, have indicated that satisfactory results are obtained if theoutlet end of the tissue cylinder is cut in a planar manner,perpendicular to the main axis of the cylinder. This can be regarded asa blunt-end or square-end cut. As an alternative method of sculpting thetissue segment, non-planar cuts (such as a mildly sinusoidal cut) can beused to generate three flaps of tissue that extend slightly beyond theoutlet ends of the longitudinal suture lines (or fixation points) or toslightly scallop the outlet end of the tube valve, as is morecharacteristic of the native semilunar valves. Non-planar outlets havenot yet been evaluated, but they can be tested using any of severaltechniques (computerized CAD-CAM analysis, in vitro testing using aclosed mechanical pumping circuit, or in vivo using animals such as dogsor sheep) to determine whether they are preferable to a square-endoutlet, either for particular patients or as a general approach.

[0117] In summary, the steps for creating a semilunar replacement valve(i.e., an aortic or pulmonary valve) can be described as follows:

[0118] 1. A tubular segment is obtained, consisting of thin and flexibletissue or synthetic material having an inlet end and an outlet end.

[0119] 2. The damaged or deformed leaflets of the native valve aresurgically removed, to generate an open valve annulus.

[0120] 3. The inlet end of the tube (or an incorporated annuloplastyring) is sutured to the valve annulus.

[0121] 4. The outlet end of the tube is sutured to the aorta orpulmonary artery at three equidistant points around the circumference.This creates three flexible tissue regions between the three points ofattachment, and the flexible tissue regions will function as valve cuspsthat will open during ventricular systole, when blood flows from theventricle into the aorta or pulmonary artery. The valve cusps willapproximate and close the valve during ventricular diastole, to preventbackflow when fluid pressure in the aorta or pulmonary artery exceedsfluid pressure in the respective ventricle.

[0122] Based on the information available to date, including animaltests as well as computer simulations and the Applicant's extensiveexperience in cardiac surgery, it appears that it is not necessary toprovide any additional safeguards to ensure that the three valve cuspsin a replacement aortic or pulmonary valve come together and closeduring each diastolic cycle, rather than being flattened against theinside of an aortic wall (or pulmonary artery wall). Nevertheless, it isrecognized that if the back pressure in the aorta were to flatten any ofthe three valve cusps against the artery wall, rather than causing allthree to close together, closure of the valve would be prevented andregurgitation (i.e., reentry of the blood into the ventricle) wouldresult. Accordingly, if it is desired to increase the level of assurancethat flattening of the cusps against the interior wall of the arterywill not occur during diastole, either as a general precaution or inpatients having certain abnormal conditions, then at least two methodsare available to reduce such risks.

[0123] The first method involves creating a partial closure of adjacentcusps at their outer periphery. This can be done by gently pinching thewalls of the inserted SIS cylinder 200 together at the outlet end ofeach of the three longitudinal suture lines 220 (or outlet attachmentpoints), as shown in FIG. 6. The pinched SIS junctures can then be heldin place by one or more suture stitches 240. If desired, the suturestitches 240 can be reinforced to prevent tearing of the SIS segment 200by placing small reinforcing pieces 242, made of a flexible, soft,blood-compatible material such as GoreTex or Silastic, on the outsidesurfaces of the SIS wall 200. As shown in FIG. 6, the pinched juncturesinclude first 243, second 244 and third 245 pinched junctures which canbe held in place, along with reinforcing pieces 242, by the suturestitches 240.

[0124] An alternate potential method for ensuring that the three cuspswill not become flattened against the inside of the aorta (or pulmonaryartery) involves a stent device that could be secured within the aorticwall 250, outside the SIS segment 200. This type of stent hasprojections which extend in an inward radial direction, toward thecentral axis of the aorta. These projections, positioned at midpointsbetween the three attachment points at the outlet end, prevent anyflattening of the cusp regions 222 against the interior of aortic wall250. This ensures that back pressure in the aorta forces each cusp in aninward direction, to ensure closure, rather than pressing the cusps inan outward direction which could cause them to flatten against theinterior of the arterial wall and allow regurgitation.

[0125] The use of such a stent probably requires placing the patient onanticoagulant drugs to reduce the risk of thrombosis. Nevertheless, theblood is not forced to flow through any mechanical elements as arecurrently used in conventional caged-ball, bi-leaflet, or tilting diskvalves; instead, the blood flows through a cusp arrangement which usessoft, flexible cusps. Therefore, this approach, even though it requiresa stent outside the cusps to ensure closure, provides a valve that isless thrombogenic and less hemolytic than any currently availablemechanical valves.

Reduction of Turbulence and Calcification by Tubular Valves

[0126] In addition to the various problems (particularly lack ofdurability) that are characteristic of conventional tissue valves in usetoday, it also appears that their designs may aggravate the problem ofcalcification, a major pathologic form of deterioration which leads tothe failure of many presently available artificial tissue valves.Previous analyses regarding the etiology of calcification of artificialtissue valves have centered around (1) the tissues used to construct thevalves, which presently are either porcine valve cusps or bovinepericardial tissue; (2) chemical fixation processes which are necessaryto render heterograft tissues non-antigenic, or (3) non-chemicalfixation processes, usually involving freezing, which are necessary totreat homograft tissues to reduce their antigenicity.

[0127] However, a highly important piece of evidence indicates thatanother factor is etiologically significant in tissue valvecalcification, namely, the turbulence of blood flow that occurs withinand around all artificial tissue valves constructed using prior artdesigns. Evidence that turbulence can cause or severely increase therisk of valve calcification in the absence of foreign material, fixationtechniques, and antigenicity, is provided by the fact that over half ofthe patients who must undergo surgery for calcific aortic stenosis wereborn with a bi-leaflet aortic valve, a condition which is notorious forcausing turbulent flow. In these patients, neither antigenicity norfixation processes can be incriminated as causes of valve calcification,since the patient's own valve is the one that has calcified. Therefore,the high rates of calcification encountered in abnormal bi-leafletaortic valves offers strong evidence that turbulent blood flow, per se,can cause or severely increase the risk of calcification of valves.

[0128] Preliminary studies suggest that by reproducing the manner inwhich native valves function, less turbulence will be generated as bloodpasses through the valves disclosed herein, compared to conventionalreplacement valves. Therefore, it appears likely that this reduction inturbulence will, in turn, reduce the likelihood that the tubular tissuevalves described herein will calcify.

Use of Intestinal Tissue in Heart Valves

[0129] To the best of the Applicant's knowledge, it has never previouslybeen disclosed or suggested that autologous human intestinal tissue,specifically the submucosa of the small intestine (SIS), can or shouldbe used to create all or part of a replacement artificial heart valve ina patient with a defective or diseased heart valve. Since autologousintestinal tissue, when harvested and treated as described above,appears to be very well suited to this use, and since it offers a numberof important advantages over materials used in conventional heart valvereplacements (including the complete absence of antigenicity, and theabsence of the requirement of chemical fixation of the tissue prior toimplantation), an important aspect of this invention is the disclosure,in broad terms, that intestinal tissue harvested from the body of thesame patient who is receiving a new heart valve can be used in thereplacement valve.

[0130] Accordingly, this invention discloses a method of surgicallyreplacing a heart valve in a human patient in need thereof, comprisingthe steps of (a) extracting a segment of intestinal tissue from thepatient's abdomen, and (b) using the intestinal tissue to form at leastone component of a replacement valve for the patient's heart. It alsodiscloses certain articles of manufacture comprising previously preparedintestinal segments, from animals or human cadavers, which have beentreated to render them suitable for use in creating replacement valves,and which are contained in sealed packages that maintain theirsterility. These articles of manufacture are discussed in more detailbelow.

Other Tissue Sources

[0131] Although autologous SIS intestinal tissue described above appearsto be an ideal tissue for creation of artificial tissue valves, thecritical factor in the construction of such artificial tissue valvesremains the tubular shape of the tissue or material to be implantedrather than the specific source of origin of that tissue or material.

[0132] Various other types of tissue from the body of the patientreceiving the heart valve replacement can be used if desired, ratherthan intestinal tissue. For example, in most patients, the pericardialsac which encloses the heart has enough tissue so that a segment can beremoved and used as a heart valve. This would allow a surgeon to conductthe entire operation without having to make an additional incision inthe patient's abdomen. In fact, recent studies by others have indicatedthe feasibility of using freshly harvested autologous pericardial tissueto create artificial cusps that can then be sutured inside the aorta toserve as an artificial aortic valve. That technique, however, differs inseveral ways from the current invention, and those investigatorsapparently have not recognized the importance of the principle that FormFollows Function. Their technique is designed to create artificial cuspsthat look like the native aortic valve cusps from fresh autologouspericardium in hopes that they will function like the native cusps. Inother words, their apparent goal and principle is to force function tofollow form,. By contrast, the subject invention states that pericardialtissue (which is essentially flat) can be used to replace an aorticvalve if desired, but the pericardium should first be fashioned into atube, and that tube should be fixed inside the aorta in the mannerdescribed above. By fixing the inlet end of the tube circumferentiallyand the outlet end of the tube at three (3) points (or along threelongitudinal lines from the inlet), the external diastolic pressure inthe aorta will cause the non-fixed sides of the tube to collapse againstone another and the pericardial tube will be forced into the shape of anormal aortic valve. In other words, “Form Follows Function”. Theprinciple that Form Follows Function will be operative in all artificialtubular valves used to replace any of the four native valves regardlessof the specific type of tissue used to create the tubes.

[0133] In view of encouraging results obtained to date with intestinaltissue, and in view of the abundant supply of small intestinal tissue inall patients, other types of autologous tissue have not been evaluatedto determine whether they are sufficiently durable and flexible for useas a heart valve. However, if the need arises, other types of autologoustissue can be evaluated using routine experimentation. For example, apotential source of tissue is the “fascia lata,” a membranous layerwhich lies on the surface of certain skeletal muscles.

[0134] Another potential source of autologous tissue is suggested by aknown phenomenon involving mechanical objects that are implanted in thebody, such as heart pacemakers. When such objects remain in the body forseveral months, they become encapsulated by a layer of smooth, ratherhomogeneous tissue. This phenomenon is described in articles such asJansen et al 1989. The cellular growth process can also be controlled bymanipulating the surface characteristics of the implanted device; seeChehroudi et al 1990. Based upon those observations and research, it ispossible that mandrel implantation in the body of a patient who willneed a heart valve replacement might become a potentially feasibletechnique for generating the cylindrical tissue.

[0135] As another potential approach, it may be possible to generateunlimited quantities of cohesive tubular tissue segments with varyingdiameters, for use in patients of different size, using in vitro tissueculture techniques. For example, extensive work has been done to developskin replacements for burn victims and tubular vascular grafts, byseeding viable connective tissue cells into lattices made of collagenfibers. Collagen is the primary protein that holds together mammalianconnective tissue, and the lattice provides the cells with anenvironment that closely emulates the environment of natural tissue. Thecells will grow to confluence, thereby forming cohesive tissue, and sometypes of cells will secrete enzymes that gradually digest the artificialcollagen matrix and replace it with newly generated collagen fiberssecreted by the cells, using the natural process of collagen turnoverand replacement. This type of cohesive tissue culture is described inarticles such as Yannas et al 1989 and Tompkins and Burke 1992.

[0136] Either of these approaches (mandrel implantation or ex vivotissue culturing) would require careful evaluation to determine whetherthe resulting tissue would be suitable for long-term use in heartvalves. With the promising results obtained to date with intestinaltissue, which is in abundant supply, there does not seem to be anapparent need to undertake such tests at the present time.

[0137] In an alternate embodiment of the subject invention, “homograft”tissue is harvested from the bodies of human cadavers for later use inartificial tubular heart valves. For example, a very long segment ofintestinal tissue comprising all or a major portion of the jejunalregion of the small intestine is resected from the body of someone whohas recently died, such as an accident victim. This harvesting operationwould be comparable to harvesting a heart, kidney, or other internalorgan from a deceased organ donor. The intestinal tissue is then cutinto segments of roughly 10 to 20 cm (four to eight inches) each, whichis prepared (by removing the serosa, smooth muscle, and submucosallayers), treated to reduce its antigenicity, and stored (at eitherrefrigerated or frozen temperature) in a sterile preservation solutionuntil use. When needed as a heart valve replacement, the tissue iswarmed and treated as necessary, and cut into the precise size andconfiguration needed.

[0138] One advantage of this approach is that it spares the cardiacpatient from any additional pain or surgical stress that might resultfrom having a surgical incision made in the abdomen to harvestautologous SIS tissue as described above. However, the additional stressor pain of obtaining a segment of intestinal tissue through a smallabdominal incision is quite small compared to open-heart surgery, wherethe chest and rib cage must be opened. Indeed, several of the newestapproaches to coronary artery bypass surgery (the most frequentlyperformed cardiac operation) require much larger abdominal incisions toharvest abdominal arteries that are now used as bypass conduits.

[0139] Another alternate embodiment is to use “heterograft” tissue fromother animal species. This embodiment probably requires chemicalfixation of the heterograft tissue (which presumably would compriseintestinal segments) by techniques such as glutaraldehyde crosslinking,as currently used to fix porcine or bovine pericardial tissue forconventional heart valve replacements. Although one might expectintestine-derived tubular tissue fixed in glutaraldehyde to haveproblems similar to the presently available tissue valves, thecalcification and durability problems of current tissue valves should besubstantially reduced because of the tubular structure of the resultantvalves, which would reproduce the function of the native valves, therebyleading to less turbulence and hence, less calcification, and greaterlong-term durability. It should also be noted that researchers arecreating, using breeding as well as genetic engineering techniques,various strains of animals (mainly pigs) that have reduced tissueantigenicity (see, e.g., Rosengard et al 1992 and Emery et al 1992).Such animals may be able to provide tissue which needs minimal fixation,or possibly no fixation treatment at all.

Tubular “Mechanical” (Non-Tissue) Valves

[0140] In addition to providing a method of using tubular human oranimal tissue to create replacement valves, this invention also suggeststhe use of tubular synthetic material as a starting material for suchvalves. Various types of highly durable and flexible synthetic materialshave been developed and are continuing to be developed, and some ofthese materials are promising candidates which can be evaluated forpossible use as described herein. One such material is sold under thetrademark “GoreTex.” It is, in essence, a polymerized layer of PTFEwhich is rendered flexible by coating it onto a flexible woven orknitted substrate material, such as nylon fabric. By coating PTFE onto atubular substrate, it is possible to create tubular forms of such coatedmaterials. Although such materials are highly durable inside the body,they can occasionally causes problems of blood clotting, apparently duein part to their rough surface textures, and possibly due also toplasticizers and other chemicals used to control the polymerization,thickness, and flexibility of the PTFE coating material.

[0141] Perfluorinated elastomers, a different class of syntheticmaterials that have recently been developed, also offer promise aspotential artificial tubular valves as described herein. Theseelastomers are described in patents such as U.S. Pat. No. 4,900,793(Lagow and Dumitru, 1990). Essentially, they contain only carbon andfluorine atoms, which are bonded together in highly stable polymericconfigurations. Perfluorinated elastomers contain very little oxygen,hydrogen, nitrogen, sulfur, or other substances that might chemicallyreact with physiological fluids to degrade the elastomer or causeleaching of constituent ions into the blood. These elastomers canprovide very smooth surfaces, and since they are elastomeric in theirown right, it is unnecessary to coat them onto the rough surface of asecond material such as woven or knitted nylon in order to provideflexibility. They can be molded or otherwise synthesized directly intotubular form.

[0142] An additional advantage that can be obtained by using syntheticmaterials in the manner disclosed herein is that an essentially tubularconfiguration can be provided which has a gradually varying diameter.For example, a relatively long tubular device can be created fromsynthetic material, having a diameter at the inlet end of up to about 5cm and a diameter at the outlet end of about 2 cm. A surgeon can simplycut the piece of tubing at any appropriate location along its length, toprovide an inlet diameter corresponding to the diameter of a patient'svalve annulus, which can be measured after the heart has been opened andthe damaged or defective leaflets have been removed. In this manner, asingle tubing size can be adapted to accommodate various differentpatients; this will reduce the costs that would be required tomanufacture or stock tubes having multiple different sizes.

[0143] In the case of artificial “mechanical” (non-tissue) tubularvalves, the more physiologic flow patterns should result in less,thrombogenicity and less turbulence, which are major problems withpresently available mechanical valves. The design disclosed herein is,to the best of the Applicant's knowledge, the only mechanical(non-tissue) valve design ever proposed that has absolutely noobstructing part within the flow orifice of the valve in the openposition. Conventional mechanical valves require hinge mechanisms,moving discs, large struts, caged balls, or bulky sewing rings, all ofwhich have been incriminated as etiologic factors in the inherentthrombogenicity and/or sub-optimal hemodynamics of previouslyconstructed mechanical heart valves, especially those of smaller sizes.Even the McGoon and Roe-Moore valve designs (described as “extinct” inBodnar and Frater 1991, pp. 319-321) required obstructions in the flowpath; those valves returned to a closed position when at rest, and theleaflets which blocked the flow path had to be forced opened in orderfor blood to flow through those valves. By contrast, the tubular valvesdisclosed herein are effectively open when at rest, and theatrioventricular leaflets or semilunar cusps close only when they areforced into a closed position by blood pressure. Compared to allpreviously available or proposed mechanical valves, the mechanicalvalves disclosed herein will have better hemodynamic characteristics andare likely to be less thrombogenic.

[0144] Finally, although the durability of conventional mechanicalvalves is considered to be their most attractive feature, valve failuresdo occur. These structural failures are invariably due to highmechanical stresses and/or trauma that are focused on certain points ina given valve design. Such repetitive, focused stresses can eventuallyresult in the failure of the materials used to construct such valves. Bycontrast, the computerized analytical studies on tubular valves,described above, indicated that the distribution of stress in a tubularreplacement valve as described herein is virtually identical to thedistribution of stress in native heart valves; such natural stressdistributions can be assumed to be optimal. Furthermore, the areas ofmaximal stress encountered by tubular replacement valves were relativelylow in magnitude, since they were distributed over larger surface areas,when compared to conventional mechanical valve designs. Therefore, thefact that tubular replacement valves are stressed in an apparentlyoptimal fashion, as dictated by nature, indicates that they will haveless risks of stress-related mechanical failure than conventionalmechanical valves.

Articles of Manufacture

[0145] In addition to disclosing a method of surgery, this inventiondiscloses an article of manufacture depicted in FIG. 7. This itemcomprises a tubular segment 500, made of tissue from the smallintestine, or synthetic material having suitable overall dimensions andwalls sufficiently thin and flexible to allow it to function as leafletsin a heart replacement valve. Since autologous tissue would not requirestorage for later use, this portion of the disclosure relates to the useof non-autologous (homograft or heterograft) tissue. This tubularsegment 500 is enclosed within a sealed container 510 that maintainssterility of the segment 500. Such a sterile container 510 can comprisea plastic pouch, as shown in FIG. 7, having a transparent front layer512 to allow visual inspection (this layer is shown folded up at onecorner, for depiction purposes only). The front layer 512 is sealedaround its periphery to a back layer 514.

[0146] In an alternate article of manufacture, depicted in FIG. 8, thetubular segment 500 is attached to an annuloplasty ring 502 before bothare sealed inside package 510. The tube-to-ring attachment can be doneby suturing in the case of tubular tissue segments, or by any suitablesynthetic method (such as molding) if a synthetic tube is attached to asynthetic annuloplasty ring.

[0147] If intestinal tissue is used, it should be packaged in hydratedform, in a suitable liquid (such as phosphate-buffered saline with oneor more preservative agents, such as glutaraldehyde, if desired)contained within the pouch. Such pouches can be shipped and stored instiff-walled boxes for protection; alternately, instead of using aflexible pouch as the container, a plastic box with a transparentclosure layer sealed around its rim can be used as the container itself.

[0148] If a segment of intestinal tissue is contained in such a sterilecontainer, it preferably should be treated before being sealed withinthe pouch, to remove the exterior serosa and muscularis layers and theinterior mucosal layer, leaving only the desirable submucosal andbasement layers.

[0149] In another preferred embodiment involving synthetic materials, asynthetic tube as described herein can have a diameter that variesgradually over its length. Such a tube can be transsected at a locationhaving the desired diameter. This would allow a tube with a single sizeto accommodate patients who have valve annulus diameters with varyingsizes.

[0150] In another preferred embodiment involving synthetic materials,different sizes of synthetic tubes can be packaged separately. Thatraises an important issue. In most cases, it will probably be possibleto directly insert an SIS intestinal segment harvested from a patientdirectly into the mitral or tricuspid valve location in that patient,since the diameters of an SIS segment and a mitral or tricuspid valveannulus in most humans is believed to be comparable or at leastcompatible. However, this does not appear top be the case with aortic orpulmonary valve replacements; in most patients, the diameter of an SISsegment is likely to be too large for direct insertion in tubular forminto the aorta or pulmonary artery of that patient. To cope with thisproblem, an SIS segment can be cut longitudinally, to convert it into aflat segment that can be trimmed to any desired size before creation ofthe replacement valve. As described above, three longitudinal suturelines can be used to create a replacement aortic or pulmonary valve, aspart of the surgical procedure. Therefore, one of these suture lines canbe used to re-size the SIS segment into a different diameter whileretaining its tubular form.

[0151] Alternately, to replace any of the four heart valves, aprepackaged intestinal tissue segment can be used which has the desireddiameter, harvested from a human cadaver or animal. This would avoid theneed for a longitudinal cut, and it would preserve the tubular form ofthe intestinal segment throughout the entire procedure. Tissue fromcadavers or animals would need to be treated by fixation (usingglutaraldehyde crosslinking or another suitable method) to reduce itsantigenicty before implantation.

[0152] Accordingly, one of the preferred embodiments of this inventioncomprises an array of sealed sterile packages containing intestinaltissue segments from cadavers or animals for use in creating replacementvalves. Each separate container would hold an intestinal segment havinga known diameter or circumference (presumably measured in millimeters),which would be indicated on the label of the container. Before beingpackaged, the tissue segments would be cleaned to remove the undesiredtissue layers and fixed to reduce antigenicity. After a surgeon opens apatient's chest and excises the cusps or leaflets from a diseased ordamaged valve, he or she can directly measure the valve annulus. Thismeasurement will indicate the exact diameter or circumference of theintestinal segment that should be used. A sealed package containing anintestinal tissue segment having the desired diameter or circumferencecan be selected and opened, and the segment will be immediatelyavailable. If desired, the tissue segment in the sterile package canalready be attached to an annuloplasty ring, which would also becontained in the package.

[0153] Synthetic material can be manufactured in tubular form by variousmeans, including extrusion, and coating (either externally orinternally) of a liquid resin, monomer, or other fluid onto acylindrical mold, followed by curing (using heat, chemicals, ultravioletradiation, etc.) of the fluid into a solidified film. The synthetic tubecan be packaged in a sterile liquid if desired, to avoid any possibilityof dehydration, cracking, flattening under pressure (which might causeformation of seams), or other degradation.

[0154] Thus, there has been shown and described a new and useful articleof manufacture and method for create replacement heart valves fromtubular tissue or synthetic material. Although this invention has beenexemplified for purposes of illustration and description by reference tocertain specific embodiments, it will be apparent to those skilled inthe art that various modifications and alterations of the illustratedexamples are possible. Any such changes which derive directly from theteachings herein, and which do not depart from the spirit and scope ofthe invention, are deemed to be covered by this invention.

References

[0155] Bailey, C. P., et al, “Use of autologous tissues in mitral valvereconstruction,” Geriatrics 25:119-129 (1970).

[0156] Bodnar, E. and Frater, R., Replacement Cardiac Valves (PergamonPress, New York, 1991).

[0157] Chehroudi, B., et al, “Titanium-coated micromachined grooves ofdifferent dimensions affect epithelial and connective-tissue cellsdifferently in vivo,” J. Biomed. Mater. Res. 24:1203-19 (1990).

[0158] David, T. E., “Mitral valve replacement with preservation ofchordae tendineae: Rationale and technical considerations,” Ann. Thorac.Surg. 41:680 (1986).

[0159] Emery, D. W., et al, “Expression of allogeneic class II cDNA inswine bone marrow cells transduced with a recombinant retrovirus,”Transplant Proc. 24:468-9 (1992).

[0160] Hansen, D. E., et al, “Relative contributions of the anterior andposterior mitral chordae tendineae to canine global left ventricularsystolic function,” J. Thorac. Cardiovasc. Surg. 93:45 (1987).

[0161] Jansen, J. A., et al, “Epithelial reaction to percutaneousimplant materials: in vitro and in vivo experiments,” J. Invest. Surg.2:29-49 (1989).

[0162] Love, C. S. and Love, J. W., “The autogenous tissue heart valve:Current Status,” J. Cardiac Surgery 6:499-507 (1991).

[0163] Mickleborough, L. L., et al, “A simplified concept for abileaflet atrioventricular valve that maintains annular-papillary musclecontinuity,” J. Cardiac Surgery 4:58-68 (1989).

[0164] Miki, S., “Mitral valve replacement with preservation of chordaetendineae and papillary muscles,” Ann. Thorac. Surg. 25:28 (1988).

[0165] Netter, F. H., The CIBA Collection of Medical Illustrations,Volume 5; The Heart (CIBA Pharm. Co., 1969).

[0166] Rittenhouse, E. A., “Replacement of ruptured chordae tendineae onthe mitral valve with autologous pericardial chordae,” J. Thorac.Cardiovasc. Surg. 75:870 (1978).

[0167] Rosengard, B. R., et al, “Selective breeding of miniature swineleads to an increased rate of acceptance of MHC-identical, but not ofclass I-disparate, renal allografts,” J. Immunol. 149:1099-103 (1992).

[0168] Tompkins, R. G. and Burke, J. F., “Burn wound closure usingpermanent skin replacement materials,” World J. Surg. 16:47-52 (1992).

[0169] Yannas, I. V., et al, “Synthesis and characterization of a modelextracellular matrix that induces partial regeneration of adultmammalian skin,” Proc. Natl. Acad. Sci. USA 86:933-937 (1989).

What is claimed is:
 1. A prosthetic heart valve; comprising: at leasttwo cusps comprised of a thin and flexible material, each cusp having aninner surface and an outer surface and being attached to another cuspalong a longitudinal suture line, each of the cusps adapted to flexinwardly into and out of engagement with another cusp so as to close andopen the valve in response to force by blood pressure; wherein a portionof the inner surface of one cusp is in a facing relationship with aportion of the inner surface of another cusp adjacent the longitudinalsuture line when the valve is open.
 2. The heart valve of claim 1,wherein the valve has an inlet end and an outlet end, and a portion ofthe inner surface of each cusp is in a facing relationship with aportion of the inner surface of each adjacent cusp adjacent thelongitudinal suture line and at the outlet end of the valve.
 3. Theheart valve of claim 1, wherein the thin and flexible material comprisespericardial tissue.
 4. The heart valve of claim 1, wherein at least onesuture holds a portion of the inner surfaces of adjacent cusps together.5. The heart valve of claim 4, wherein the inner surfaces of adjacentcusps are held together toward the out-flow end of the valve so that thecusps are biased partially closed even when the valve is generally open.6. The heart valve of claim 4 additionally comprising suturereinforcements.
 7. A method for making a prosthetic heart valve,comprising: providing a section of substantially flat, flexiblematerial; cutting at least two leaflets out of the flat material, eachof the leaflets having an inner face, an outer face, an in-flow end, anout-flow end, and side edges; sewing the side edges of adjacent leafletstogether so as to form a substantially tubular valve structure having anin-flow end and an out-flow end; and configuring each leaflet so that aportion of the inner face of each leaflet is in a facing relationshipwith a portion of the inner face of an adjacent leaflet.
 8. The methodof claim 7, wherein a portion of the inner face of each leaflet is in afacing relationship with a portion of the inner face of another leafletat the out-flow end of the valve so that the adjacent leaflets arepartially closed.
 9. The method of claim 7 additionally comprisinginstalling a suture stitch through each leaflet to hold a portion of theinner face of the leaflet in a facing relationship with a portion of theinner face of an adjacent leaflet.
 10. The method of claim 9additionally comprising providing reinforcements for the suturestitches.
 11. The method of claim 7, comprising pinching adjacentleaflets together so that a portion of the inner faces of the adjacentleaflets are in facing relationship with each other.
 12. The method ofclaim 11, wherein the adjacent leaflets are pinched together at theout-flow end so as to create partial closure of the adjacent leaflets.